Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969    43 KSQESAAGSKLVLRCETSSeYSSLRFKWFKNGNELnrKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDS 122
Cdd:smart00410   2 PSVTVKEGESVTLSCEASG-SPPPEVTWYKQGGKL--LAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*..
gi 236463969   123 ASANITI 129
Cdd:smart00410  79 SGTTLTV 85

IL-1 receptor-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 236463969  60 SSEYSSLRFKWFKNGNELnrknkPQNIKIQKKPGKSELRINKASLADSGEYMCKVisKLGNDSASANIT 128
Cdd:PHA02826 158 SSTFKDYTLTWYKNGNIV-----LYTDRIQLRNNNSTLVIKSATHDDSGIYTCNL--RFNKNSNNYNIT 219

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  37 PRLKEMKSQESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKnKPQNIKIQKKPGKSELRINKASLADSGEYMCKVIS 116
Cdd:cd05750    1 PKLKEMKSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRK-RPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVEN 79

                         90
                 ....*....|...
gi 236463969 117 KLGNDSASANITI 129
Cdd:cd05750   80 ILGKDTVTGNVTV 92

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969   39 LKEMKSQESAAGSKLVLRCETSsEYSSLRFKWFKNGNELNRKNKpqnIKIQKKPGKSELRINKASLADSGEYMCKVISKL 118
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDR---FKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 236463969  119 GNDSASANITI 129
Cdd:pfam07679  80 GEAEASAELTV 90

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969   43 KSQESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKNKPQniKIQKKPGKSELRINKASLADSGEYMCKVISKLGNDS 122
Cdd:pfam00047   4 PTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVK--HDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81

                  ....*
gi 236463969  123 ASANI 127
Cdd:pfam00047  82 LSTSL 86

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 236463969  53 LVLRCETSSeYSSLRFKWFKNGNELNRKNKPqniKIQKKPGKSELRINKASLADSGEYMCKVISKL-GNDSASA 125
Cdd:cd00096    1 VTLTCSASG-NPPPTITWYKNGKPLPPSSRD---SRRSELGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  39 LKEMKSQESAAGSKLVLRCETSSEySSLRFKWFKNGNELNRKNKpqnikIQKKPGKseLRINKASLADSGEYMCKVISKL 118
Cdd:cd05728    3 LKVISDTEADIGSSLRWECKASGN-PRPAYRWLKNGQPLASENR-----IEVEAGD--LRITKLSLSDSGMYQCVAENKH 74

                         90
                 ....*....|.
gi 236463969 119 GNDSASANITI 129
Cdd:cd05728   75 GTIYASAELAV 85

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  48 AAGSKLVLRCETSSEYSSLrFKWFKNGNELNRKNkpQNIKIQKKpgkSELRINKASLADSGEYMCKVISKLGNDSASANI 127
Cdd:cd20952   12 AVGGTVVLNCQATGEPVPT-ISWLKDGVPLLGKD--ERITTLEN---GSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85

                 ..
gi 236463969 128 TI 129
Cdd:cd20952   86 DV 87

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  37 PRLKEMKSQESAAGSKLVLRCETSSE-YSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVI 115
Cdd:cd05732    3 PKITYLENQTAVELEQITLTCEAEGDpIPEITWRRATRGISFEEGDLDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEAS 82

                 ....*....
gi 236463969 116 SKLGNDSAS 124
Cdd:cd05732   83 NRIGGDQQS 91

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 236463969  69 KWFKNGNELNRKNKPQNIkiQKKPGKSELRINKASLADSGEYMCKVISKLGNDSASANITI 129
Cdd:cd20973   30 KWMKDDNPIVESRRFQID--QDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-2 and -1 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  43 KSQESAAGSKLVLRCETSSEYSS-LRFKW-FKNGNELNRKNKPQNIKIQKKPGK---SELRINKASLADSGEYMCKVISK 117
Cdd:cd05862    9 KPVELLVGEKLVLNCTARTELNVgVDFQWdYPGKKEQRRASVRRRRKQQSSEATefsSTLTIDNVTLSDKGLYTCAASSG 88

                         90
                 ....*....|....
gi 236463969 118 LGNDSASANITIVE 131
Cdd:cd05862   89 PMFKKNSTSVIVHE 102

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  34 ALPPRLkemksqESAAGSKLVLRCeTSSEYSSLRFKWFKNGNELNRKNKpqniKIQKKPGKSELRINKASLADSGEYMCK 113
Cdd:cd20976    6 SVPKDL------EAVEGQDFVAQC-SARGKPVPRITWIRNAQPLQYAAD----RSTCEAGVGELHIQDVLPEDHGTYTCL 74

                         90
                 ....*....|....*.
gi 236463969 114 VISKLGNDSASANITI 129
Cdd:cd20976   75 AKNAAGQVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  35 LPPRLKEMKSQesaaGSKLVLRCETSSEYSS-LRFKWFKNGNELNRKNKPQ-NIKIQKKPGK---SELRINKASLADSGE 109
Cdd:cd05742    6 SPNAEPTVLPQ----GETLVLNCTANVNLNEvVDFQWTYPSEKEGKLALLKpDIKVDWSEPGefvSTLTIPEATLKDSGT 81

                         90       100
                 ....*....|....*....|.
gi 236463969 110 YMCKVISKLGNDSASANITIV 130
Cdd:cd05742   82 YTCAARSGVMKKEKQTSVSVH 102

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  43 KSQESAAGSKLVLRCETSSEYSSLRFKWF--------------KNGNELNRKNKPQNIKIQKKPGKS-ELRINKASLADS 107
Cdd:cd00099    6 RSLSVQEGESVTLSCEVSSSFSSTYIYWYrqkpgqgpefliylSSSKGKTKGGVPGRFSGSRDGTSSfSLTISNLQPEDS 85

                         90
                 ....*....|....
gi 236463969 108 GEYMCKVISKLGND 121
Cdd:cd00099   86 GTYYCAVSESGGTD 99

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969   43 KSQESAAGSKLVLRCETSSEYS--SLRFKW---------------FKNGNELNRKnkPQNIKIQKKPGKS--ELRINKAS 103
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSeaSTSVYWyrqppgkgptfliayYSNGSEEGVK--KGRFSGRGDPSNGdgSLTIQNLT 81

                          90
                  ....*....|....
gi 236463969  104 LADSGEYMCKVISK 117
Cdd:pfam07686  82 LSDSGTYTCAVIPS 95

Sixth immunoglobulin (Ig) domain of contactin-4; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-4. Contactins are neural cell adhesion molecules, and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. Highest expression of contactin-4 is in testes, thyroid, small intestine, uterus, and brain. Contactin-4 plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. The contactin 4 gene is associated with cerebellar degeneration in spinocerebellar ataxia type 16.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  44 SQESAAGSKLVLRCETSSEYS-SLRFKWFKNGNELN-RKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGND 121
Cdd:cd05853   11 SMDVTVGESIVLPCQVSHDHSlDIVFTWSFNGHLIDfQKDGDHFERVGGQDSAGDLMIRSIQLKHAGKYVCMVQTSVDKL 90

                 ....*...
gi 236463969 122 SASANITI 129
Cdd:cd05853   91 SAAADLIV 98

First immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  37 PRLKEMKSQ----ESAAGsklVLRCETSSEYSSLRFKWFKNGNELNRKNkpQNIKIQKKPGKSELRINKASlaDSGEYMC 112
Cdd:cd20979    1 PVLKEQPAEvlfrEGQPT---VLECVTEGGDQGVKYSWLKDGKSFNWQE--HNVAQRKDEGSLVFLKPQAS--DEGQYQC 73

                         90
                 ....*....|...
gi 236463969 113 KVISKLGNDSASA 125
Cdd:cd20979   74 FAETPAGVASSRV 86

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 236463969  49 AGSKLVLRCETSSEySSLRFKWFKNGNELNRKNKPQNIKIQKKpgKSELRINKASLADSGEYMCKVISKLGNDSASANIT 128
Cdd:cd05729   18 AANKVRLECGAGGN-PMPNITWLKDGKEFKKEHRIGGTKVEEK--GWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVD 94

                 .
gi 236463969 129 I 129
Cdd:cd05729   95 V 95